Enabling NGS-Based Product Characterization and Biosafety Assays in GxP Environments | Part 2

March 14, 2024
Valentina Armiento

Welcome to the second part of this comprehensive series on Next-Generation Sequencing (NGS) in biopharmaceutical drug development and manufacturing. The first part investigated the increasing adoption of NGS, the guidelines established by the regulatory authorities for its use, and the role of Genedata Selector^® in simplifying and accelerating complex NGS-based data analysis workflows in a validated environment.

One of the challenges biopharmaceutical companies are facing is the practical implementation of regulatory guidelines for entering the validated environment. Genedata Selector, with its GxP-compliant functionalities, stands as an effective tool for Computerized System Validation (CSV) projects. It is designed to handle complex NGS data, providing a unified platform for seamless data integration, management, and analysis. Its robustness and scalability make it suitable for high-throughput NGS data processing, thereby facilitating efficient and reliable biotherapeutic development. Genedata Selector is equipped with advanced data security and traceability features, which are critical for maintaining data integrity in a GxP environment. In addition to the software platform, the Genedata team offers validation support services that can assist biopharmaceutical organizations in their validation journey.

NGS technology is widely used in biosafety and product characterization of therapies due to its high sensitivity. It is expected that classical non-NGS-based assays will be replaced by NGS technology-based assays. This shift expedites delivery timelines to patients while ensuring the quality and safety of products. However, the implementation of NGS methods in a validated environment is a work in progress. The FDA has provided guidelines outlining the steps to design, execute, and validate NGS-based testing.^1-2 Furthermore, the International Council for Harmonization (ICH) of Technical Requirements for Pharmaceuticals for Human Use has issued the ICHQ5A (R2) guideline, which will come into effect on June 14, 2024.³ This guideline recommends the use of NGS technology as a complementary in vitro cell-based infectivity assay to the in vivo animal testing assay, reducing the need for animal testing. Biopharmaceutical companies that are eager to use NGS-based assays in the GMP environment must validate their computerized systems and implement a flexible and adaptable solution that allows the validation of multiple NGS assays derived from different methods, instruments, protocols, and facilities.

Read Blog Part 1

A Key Requirement for Assay Validation: Computerized System Validation

Computerized System Validation (CSV) is a crucial aspect of the overall assay validation process that pharmaceutical companies need to address, from development to commercial manufacturing. CSV is used to test, validate, and qualify a computerized system, ensuring that it performs its intended functions in a consistent and reliable manner. CSV is a digitalization prerequisite when replacing traditional paper-based documentation systems with computerized systems, allowing the recording of activities, and creating traceable and unalterable data trails that are safely stored and can be accessed anytime. This key requirement was also confirmed by a poll conducted during the 8th Genedata Selector NGS Open Forum. Digitalization is a thorough, systematic, and interdisciplinary process that requires meticulous planning, diligent effort, and documentation to ensure that the computerized systems are validated and can be used with confidence within the GMP environment.
The basic requirements for validating electronic signatures and records are described in the Code of Federal Regulations (CFR) under FDA 21 CFR Part 11. This regulation includes requirements for validation, audit trails, legacy systems, copies of records, and records retention to ensure secure and reliable records.⁴ An important guideline is Good Automated Manufacturing Practice (GAMP) 5, which provides a structural framework that emphasizes risk-based validation to ensure the reliability, consistency, and compliance of computerized systems.⁵ Essential elements of the qualification process of computerized systems are the documented and executable Installation Qualification (IQ), Operational Qualification (OQ), and Performance Qualification (PQ) protocols. The IQ confirms the correct installation of the software and the hardware according to the specifications. The OQ (also known as functional verification) covers testing system functionalities to confirm that they perform correctly as specified. PQ is the final step of validation, and it focuses on demonstrating that the computer system works as expected, fits the intended purpose, and meets the user’s needs.

Streamlining NGS-Based Assay Validation Implementation

Relying on an outsourced service provider offering NGS-based assay under GMP poses challenges. The client may lose control of the process, and based on previous experiences, the turn-around time can take multiple weeks and is not consistent. Proper processing of the samples requires the sharing of confidential information, and a scalable solution is necessary for in-process control of upcoming sample throughput. To overcome the challenges of validating NGS-based assays, the best solution is to validate an end-to-end in-house enterprise platform that supports multiple NGS assays. This approach enables full automation from sample registration to report sign-off in a validated environment, simplifying the assay development and validation process. It also improves user experience, ensures consistency and reliability in data analysis, and streamlines operations within and across therapeutic modalities, applications, and facilities.
With extensive expertise and collaborations with industrial partners, the Genedata Selector team has years of experience in developing tailored and sensitive validation-ready solutions for NGS-based assays. Genedata Selector is an end-to-end solution that can be easily integrated into the GMP environment to provide 21 CFR Part 11- compliant reports to regulatory affairs. The platform enables standardized data management, processing, analysis, and interpretation of data, as well as quality control, and report generation. By utilizing Genedata Selector, companies can streamline the NGS-assay validation process in-house and ensure high efficiency and compliance with regulatory requirements. The results of the poll conducted at the 8th Genedata Selector NGS Open Forum underscored the significance of operating software in a validated environment for biopharmaceutical industries. Specifically, this poll highlighted the need for quality assurance (QA) teams to access guidelines from regulatory authorities and use validation-ready workflows to establish NGS-based assays within a GMP environment. This underscores the importance of adhering to regulatory standards and best practices to ensure the safety, efficacy, and quality of biopharmaceutical products.
The validation – an interdisciplinary collaborative process between the Genedata team and its industrial partner – requires two steps. The first one is to build the foundation through system validation. This includes the comprehensive documentation and validation of the Genedata Selector system architecture as the platform that supports all the GMP operations. In the second step, the assay validation is carried out by standardizing the parameters of sample preparation, nucleic acid extraction, sequencing library preparations, and setting up information tracking by the Genedata Selector platform. Selected parameters will be used to automate workflows and configure the assay-specific Genedata Selector Playbooks as end-to-end solutions under GMP.
The validated operational platform can then support multiple assays and Playbooks that underlie the same validation framework, speeding up timelines and allowing a connection between the QA personnel and bioinformaticians. Genedata supports the deployment of the platform throughout the validation process and its maintenance.

Genedata Selector, a GxP-compliant tool, streamlines CSV projects by managing and analyzing complex NGS data. Its advanced features ensure data integrity, enabling efficient NGS processing and biotherapeutic development.

Download Full Infographic

Conclusion

NGS-based assays are increasingly being utilized for biosafety and product characterization of therapies. However, their deployment in a GMP environment can be challenging. To overcome these challenges, it is recommended to validate an in-house platform that supports multiple NGS assays. The Genedata Selector team has extensive expertise and provides a comprehensive solution that enables implementation into a GMP environment. This ensures compliance with regulatory requirements during the validation process. By validating the system and assays, Genedata Selector becomes a platform of choice for many biopharma companies across biologics and CGT, as it supports multiple modalities, and types of NGS assays, streamlining operations and ensuring data consistency and reliability.

References

Food and Drug Administration (FDA). Use of Public Human Genetic Variant Databases to Support Clinical Validity for Genetic and Genomic-Based In Vitro Diagnostics. (2018).
Food and Drug Administration (FDA). Considerations for Design, Development, and Analytical Validation of Next Generation Sequencing (NGS) - Based In Vitro Diagnostics (IVDs) Intended to Aid in the Diagnosis of Suspected Germline Diseases. (2018).
International Council for Harmonisation (ICH), European Medicines Agency (EMA). Viral Safety Evaluation Of Biotechnology Products Derived from Cell Lines of Human or Animal Origin Q5A(R2). (2023).
Food and Drug Administration (FDA). Part 11, Electronic Records; Electronic Signatures - Scope and Application. (2003)
International Society for Pharmaceutical Engineering (ISPE). GAMP^® 5: A Risk-Based Approach to Compliant GxP Computerized Systems. (2022)